Recent work from our laboratory indicates that the size distribution and structure of the zymogen granule of the pancreas may vary with physiological state. The zymogen granule has generally been assumed to be constant in size and of unitary structure. However, granules in the newborn are extremely large and undergo dramatic decreases in size during the first weeks of postnatal life. A similar but less dramatic decrease in granule size is seen in adult rats with feeding after a prolonged fast. We intend to analyze the zymogen granule size distribution during the first three weeks of postnatal life and in the adult pancreas after feeding and stimulation with a pharmacological agent. We also plan to measure the turnover of zymogen granules in the postnatal pancreas and correlate the turnover with changes in size distribution. Changes in granule size have not been appreciated in the past and may have an important impact on our understanding of the way in which the pancreas secretes digestive enzymes. These studies bear upon the mechanisms of transport of secretory products in general, compare and test current hypotheses regarding these mechanisms.